Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-κB activation

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dc.contributor.author O'Mahony, Caitlin
dc.contributor.author Scully, Paul
dc.contributor.author O'Mahony, David
dc.contributor.author Murphy, Sharon
dc.contributor.author O'Brien, Frances
dc.contributor.author Lyons, Anne
dc.contributor.author Sherlock, Graham
dc.contributor.author MacSharry, John
dc.contributor.author Kiely, Barry
dc.contributor.author Shanahan, Fergus
dc.contributor.author O'Mahony, Liam
dc.contributor.editor Ausubel, Frederick M.
dc.date.accessioned 2012-12-12T11:37:47Z
dc.date.available 2012-12-12T11:37:47Z
dc.date.copyright 2008
dc.date.issued 2008-08-01
dc.identifier.citation O’Mahony C, Scully P, O’Mahony D, Murphy S, O’Brien F, et al. (2008) Commensal-Induced Regulatory T Cells Mediate Protection against Pathogen-Stimulated NF-kB Activation. PLoS Pathog 4(8): e1000112. doi:10.1371/journal.ppat.1000112 en
dc.identifier.volume 4 en
dc.identifier.issued 8 en
dc.identifier.startpage e1000112 en
dc.identifier.issn 1553-7366
dc.identifier.issn 1553-7374
dc.identifier.uri http://hdl.handle.net/10468/847
dc.identifier.doi 10.1371/journal.ppat.1000112
dc.description.abstract Host defence against infection requires a range of innate and adaptive immune responses that may lead to tissue damage. Such immune-mediated pathologies can be controlled with appropriate T regulatory (Treg) activity. The aim of the present study was to determine the influence of gut microbiota composition on Treg cellular activity and NF-kB activation associated with infection. Mice consumed the commensal microbe Bifidobacterium infantis 35624 followed by infection with Salmonella typhimurium or injection with LPS. In vivo NF-kB activation was quantified using biophotonic imaging. CD4+CD25+Foxp3+ T cell phenotypes and cytokine levels were assessed using flow cytometry while CD4+ T cells were isolated using magnetic beads for adoptive transfer to naı¨ve animals. In vivo imaging revealed profound inhibition of infection and LPS induced NF-kB activity that preceded a reduction in S. typhimurium numbers and murine sickness behaviour scores in B. infantis–fed mice. In addition, pro-inflammatory cytokine secretion, T cell proliferation, and dendritic cell co-stimulatory molecule expression were significantly reduced. In contrast, CD4+CD25+Foxp3+ T cell numbers were significantly increased in the mucosa and spleen of mice fed B. infantis. Adoptive transfer of CD4+CD25+ T cells transferred the NF-kB inhibitory activity. Consumption of a single commensal micro-organism drives the generation and function of Treg cells which control excessive NF-kB activation in vivo. These cellular interactions provide the basis for a more complete understanding of the commensal-host-pathogen trilogue that contribute to host homeostatic mechanisms underpinning protection against aberrant activation of the innate immune system in response to a translocating pathogen or systemic LPS. en
dc.description.sponsorship Science Foundation Ireland (SFI-CSET) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher PLOS en
dc.relation.uri http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000112
dc.rights © 2008 O'Mahony et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en
dc.rights.uri http://creativecommons.org/licenses/by/2.5/ en
dc.subject Regulatory T Cells en
dc.subject Bifidobacterium infantis en
dc.subject Salmonella typhimurium en
dc.subject Commensal en
dc.subject Pathogen en
dc.subject NF-kB en
dc.subject.lcsh T cells en
dc.title Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-κB activation en
dc.type Article (peer-reviewed) en
dc.internal.authorurl http://research.ucc.ie/profiles/C012/fshanahan en
dc.internal.authorcontactother Fergus Shanahan, Alimentary Pharmabiotic Centre, Biosciences Building, University College Cork, Cork, Ireland, E-mail: f.shanahan@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.internal.rssid 89608576
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Health Research Board en
dc.contributor.funder Higher Education Authority en
dc.contributor.funder Alimentary Health Ltd, Ireland en
dc.description.status Peer reviewed en
dc.identifier.journaltitle PLoS Pathogens en
dc.internal.copyrightchecked This is a Sherpa Romeo Green Journal. Policy: The Public Library of Science (PLOS) applies the Creative Commons Attribution License (CC-BY) to works we publish (read the human-readable summary or the full license legal code). Under this license, authors retain ownership of the copyright for their content, but allow anyone to download, reuse, reprint, modify, distribute, and/or copy the content as long as the original authors and source are cited. No permission is required from the authors or the publishers. Appropriate attribution can be provided by simply citing the original article. For any reuse or redistribution of a work, users must also make clear the license terms under which the work was published. This broad license was developed to facilitate free access to, and unrestricted reuse of, original works of all types. Applying this standard license to your own work will ensure that it is freely and openly available in perpetuity. en
dc.internal.IRISemailaddress f.shanahan@ucc.ie en


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© 2008 O'Mahony et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Except where otherwise noted, this item's license is described as © 2008 O'Mahony et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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